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Ontogeny of CD4+ T Lymphocytes with Phenotypic Susceptibility to HIV-1 during Exclusive and Non-Exclusive Breastfeeding in HIV-1-exposed Ugandan Infants.

Ontogeny of CD4+ T Lymphocytes with Phenotypic Susceptibility to HIV-1 during Exclusive and Non-Exclusive Breastfeeding in HIV-1-exposed Ugandan Infants.
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McFarland EJ, Powell TM, Onyango-Makumbi C, Zhang W, Melander K, Naluyima P, Okurut S, Eller MA, Fowler MG, Janoff EN,


McFarland EJ, Powell TM, Onyango-Makumbi C, Zhang W, Melander K, Naluyima P, Okurut S, Eller MA, Fowler MG, Janoff EN, (click to view)

McFarland EJ, Powell TM, Onyango-Makumbi C, Zhang W, Melander K, Naluyima P, Okurut S, Eller MA, Fowler MG, Janoff EN,

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The Journal of infectious diseases 2016 12 08() pii

Abstract
BACKGROUND
Among HIV-1-exposed infants, mixed breastfeeding is associated with higher postnatal HIV-1 transmission than exclusive breastfeeding, but the mechanisms of this differential risk are uncertain.

METHODS
HIV-1-exposed, Ugandan infants were prospectively assessed over the first year of life for feeding practices and T cell maturation, intestinal homing (β7(hi)), activation, and HIV-1 co-receptor (CCR5) expression in peripheral blood. Infants receiving only breast milk and those with introduction of other foods prior to 6 months, categorized as exclusive and non-exclusive, respectively.

RESULTS
Among CD4(+) and CD8(+) T cells, the expression of memory, activation and CCR5 markers increased rapidly from birth to week 2, peaking at week 6 whereas cells expressing the intestinal homing marker increased steadily in the central memory (CM) and effector memory (EM) T cells over 48 weeks. At 24 weeks, when feeding practices had diverged, non-exclusively breastfed infants showed increased frequencies and absolute counts of β7(hi) CM CD4(+) and CD8(+) T cells, including the HIV-1-targeted cells co-expressing CD4(+)β7(hi)/CCR5(+), as well as increased activation.

CONCLUSIONS
The T cell phenotype associated with susceptibility to HIV-1 infection (CCR5(+), gut-homing, central memory CD4(+) T cells) was preferentially expressed in non-exclusively breastfed infants, a group of infants at increased risk for HIV-1 acquisition.

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